Jennine Lunetta - Academia.edu (original) (raw)

Papers by Jennine Lunetta

Research paper thumbnail of Molecular Cloning and Expression of a cDNA Encoding a Coccidioides posadasii Cu,Zn Superoxide Dismutase Identified by Proteomic Analysis of the Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, Mar 1, 2007

Research paper thumbnail of Molecular cloning and expression of a cDNA encoding a Coccidioides posadasii 1,2-alpha-mannosidase identified in the coccidioidal T27K vaccine by immunoproteomic methods

Annals of the New York Academy of Sciences, Oct 1, 2007

Research paper thumbnail of Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal

Molecular Pharmacology

Administration of the allylbarbiturate secobarbital (SB) to phenobarbital-pretreated rats is know... more Administration of the allylbarbiturate secobarbital (SB) to phenobarbital-pretreated rats is known to result in structural and functional loss of hepatic cytochrome P-450 and generation of N-alkylated prosthetic heme derivatives. Isozyme-selective functional markers have led us to confirm P-450b as the isozyme selectively inactivated by the drug. In contrast to its inactivation by allylisopropylacetamide, such SB-inactivated P-450b is not amenable to structural and functional repair by exogenous heme, for reasons that remain unclear. In an effort to gain some insight, we have explored various possible mechanisms. In the course of these studies with rat liver microsomes enriched in P-450b as well as isolated purified P-450b, we have found that, along with prosthetic heme alkylation, a significant fraction of the hemoprotein also undergoes drug-mediated alkylation of the apocytochrome, presumably at the active site. Accordingly, an equimolar ratio of irreversibly bound drug to functio...

Research paper thumbnail of Solid-phase extraction protocol for isolating retinol-d4 and retinol from plasma for parallel processing for epidemiological studies

Clinical Chemistry

Solid-phase extraction permits the parallel processing of samples in large numbers. We have appli... more Solid-phase extraction permits the parallel processing of samples in large numbers. We have applied this technique to the isolation of retinol isotopomers from plasma of humans participating in a study of vitamin A stable isotope dilution. The isotopomers were analyzed by gas chromatography/mass spectrometry. The extraction involves the separation of retinol from its aqueous matrix with a C18 silica-based sorbent followed by removal of lipid contaminants with an aminopropyl silica-based sorbent. Overall recovery of retinol from plasma was 47.2% +/- 1.8%. Purity of the retinol isolated from plasma is comparable with that obtained with a single HPLC method. This method permits the preparation of 32 samples per day by one analyst. Elimination of the need for HPLC permits sample preparation in the field with a minimum of equipment and technical skill.

Research paper thumbnail of Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils

PloS one, 2015

Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (... more Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever) in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis) as well as upon contact (by serum-dependent adhesion and phagocytosis). This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under ...

Research paper thumbnail of Identification, molecular characterization, and expression analysis of a DOMON-like type 9 carbohydrate-binding module domain-containing protein of Coccidioides posadasii

Medical mycology, 2014

Previously, we investigated the effect of N-acetylglucosamine (GlcNAc) on Coccidioides posadasii ... more Previously, we investigated the effect of N-acetylglucosamine (GlcNAc) on Coccidioides posadasii chitinolytic enzymes during in vitro spherule-endospore (S/E) phase culture. During those studies, sodium dodecyl sulfatepolyacrylamide gel electrophoresis analysis of supernatants from S/E phase cultures grown in Converse medium with or without added GlcNAc revealed a ∼ 28-kDa band (CFP28), whose abundance was increased by GlcNAc in parallel with the chitinolytic enzymes. Mass spectrometry (MS) of the CFP28 band revealed peptides that matched an open reading frame found in the tentative consensus sequence, TC20325, retrieved from the Dana Farber Cancer Institute C. posadasii Gene Index Database. The TC20325 cDNA sequence was used to design internal primers based on MS peptides and a full-length cDNA was isolated using a combination of rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. The deduced amino acid sequence of the full-length cDNA consists of ...

Research paper thumbnail of The active sites of cytochromes P450 IA1, IIB1, IIB2, and IIE1. Topological analysis by in situ rearrangement of phenyl-iron complexes

The Journal of biological chemistry, Jan 15, 1991

The reactions of cytochromes P450 IA1, IIB1, IIB2, and IIE1 with phenyldiazene yield complexes wi... more The reactions of cytochromes P450 IA1, IIB1, IIB2, and IIE1 with phenyldiazene yield complexes with absorption maxima at either 474 or 480 nm. Anaerobic extraction of the prosthetic group from the phenyldiazene-treated proteins followed by its exposure to oxygen and strong acid produces an equal mixture of the four possible N-phenylprotoporphyrin IX regioisomers. Exposure of the anaerobically extracted heme complexes to oxygen in the absence of strong acid results in their decomposition to heme and products other than N-phenylprotoporphyrin IX. These results show that the 474/480 nm absorption maxima are due to sigma phenyl-iron complexes. Treatment of the intact hepatic cytochrome P450 complexes with K3Fe(CN)6 results in disappearance of the 474/480 nm band. Extraction of the prosthetic group then yields only the two N-phenylprotoporphyrin IX regioisomers with the N-phenyl group on pyrrole rings A and D. The same regioisomer pattern is obtained if the cytochrome P450IA1 phenyl-iron...

Research paper thumbnail of Latency-Associated Sense Transcripts Are Expressed during in Vitro Human Cytomegalovirus Productive Infection

Virology, 2000

Published studies have identified novel sense transcripts in latent human cytomegalovirus (HCMV) ... more Published studies have identified novel sense transcripts in latent human cytomegalovirus (HCMV) infection. These cytomegalovirus latency-associated transcripts (CLTs) have start sites upstream from the MIE gene productive start site (PSS). We evaluated the expression of the sense CLTs in an in vitro HCMV productive infection. Transcripts with initiation sites upstream from the PSS were detected in infected human fibroblasts using reverse transcription-polymerase chain reaction and 5' rapid amplification of cDNA ends (RACE) analysis. DNA sequencing of 5' RACE PCR products confirmed that the start sites were consistent with sense CLT expression. Furthermore, ribonuclease protection assay analysis showed that transcripts initiating at the latent start site-1 were most abundant at late times postinfection after transcription from the PSS had decreased. In addition, transcription consistent with sense CLT expression was identified in HCMV-infected dTHP-1 cells, monocyte-derived macrophages, and endothelial cells, as well as in clinical isolate-infected human fibroblasts. These findings clearly demonstrate the expression of sense CLTs during in vitro HCMV infection.

Research paper thumbnail of Molecular cloning, characterization and expression analysis of two β-N-acetylhexosaminidase homologs of Coccidioides posadasii

Research paper thumbnail of Racial Differences in Clinically Localized Prostate Cancers of Black and White Men

The Journal of Urology, 1998

Purpose: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression... more Purpose: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences.

Research paper thumbnail of Early Treatment With Fluconazole May Abrogate the Development of IgG Antibodies in Coccidioidomycosis

Clinical Infectious Diseases, 2011

Background. We have observed a number of patients who fail to develop coccidioidal complement fix... more Background. We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease.

Research paper thumbnail of Drug-Induced Modulations of Hepatic Heme Metabolism Neurological Consequences

Annals of the New York Academy of Sciences, 1987

Research paper thumbnail of Molecular Cloning and Expression of a cDNA Encoding a Coccidioides posadasii Cu,Zn Superoxide Dismutase Identified by Proteomic Analysis of the Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, 2007

Research paper thumbnail of Characteristics of the Protective Subcellular Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, 2007

While the whole killed spherule vaccine, protective in mice and monkeys, did not prevent coccidio... more While the whole killed spherule vaccine, protective in mice and monkeys, did not prevent coccidioidal disease in humans, the 27K vaccine, a soluble derivative, retains protective activity in mice with little irritant action. Gel filtration and anion exchange fractions of thimerosal-inactivated spherules (T27K), when administered with alum adjuvant, also protect mice against lethal respiratory coccidioidal challenge. However, the superb protection afforded by T27K antigens is maintained for some 3 months, but may then diminish. This appears unrelated to the aging of the mice. Prolongation of the protective action may require addition of a different adjuvant or administration of booster doses of vaccine.

Research paper thumbnail of Method for the Simultaneous Determination of Retinol and β-Carotene Concentrations in Human Tissues and Plasma

Analytical Biochemistry, 2002

To understand differential tissue distribution of retinoids and carotenoids, as it might influenc... more To understand differential tissue distribution of retinoids and carotenoids, as it might influence biological processes in humans, we developed and demonstrated a method for measuring them in selected human tissues. The method includes internal standards and a secondary reference standard to eliminate the need for external standard calibration and to minimize sample-handling errors. Tissues were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were extracted with organic solvent containing internal standards. Analytes were separated using isocratic liquid chromatography and quantified at 325 nm for retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t-butyloxime served as internal standards. Plasma, breast, and fat from breast surgery patients and colon, liver, muscle, and fat from colon surgery patients were analyzed. Within-day relative standard deviations (RSDs) for plasma were <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for beta-carotene and <0.04 for retinol. Saponification ensured complete extraction of retinol and beta-carotene and removal of triglycerides that "foul" chromatographic columns. It seems retinol and beta-carotene concentrations in tissues and blood of cancer patients are the same or higher than those in corresponding tissues of patients without these cancers.

Research paper thumbnail of Identification, Molecular Characterization and Evaluation of Some Ruminal Bacteria That Catalyze and Degrade Plant Cellulosic Materials

American Journal of Applied Sciences, 2014

Research paper thumbnail of Behavioral and neurochemical changes in folate-deficient mice

Physiology & Behavior, 1995

changes in folate-deficient mice. PHYSIOL BEHAV 58(5) 935-941, 1995.--Weanling mice were fed an a... more changes in folate-deficient mice. PHYSIOL BEHAV 58(5) 935-941, 1995.--Weanling mice were fed an amino acid-based diet supplemented with 0 or 11.3 /.~mol folic acid/kg diet for ~ 38 days to study behavior and neurochemistry in folate deficiency. After ~ 5 wk, mice fed the unsupplemented diet weighed ~ 70% as much those fed the supplemented diet. After 2 wk, mice fed the unsupplemented diet consistently discarded (spilled) more food, and after ~ 5 wk, they had spilled 3 times more than mice fed the supplemented diet. Serum folate, brain folate and brain S-adenosylmethionine of mice fed the unsupplemented diet were 4, 53, and 60% as high, respectively, as those of mice fed the supplemented diet. Pathologic changes were not evident in brain, spinal cord, or skeletal muscle of folate-deficient mice. The hypothalamic 5-hydroxyindole acetic acid/serotonin ratio and caudate dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations were lower in deficient than control mice. Folate-deficient mice develop a behavioral activity, food spilling, which may have a neurochemical basis in the serotonin and dopamine systems.

Research paper thumbnail of Molecular Cloning and Expression of a cDNA Encoding a Coccidioides posadasii Cu,Zn Superoxide Dismutase Identified by Proteomic Analysis of the Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, Mar 1, 2007

Research paper thumbnail of Molecular cloning and expression of a cDNA encoding a Coccidioides posadasii 1,2-alpha-mannosidase identified in the coccidioidal T27K vaccine by immunoproteomic methods

Annals of the New York Academy of Sciences, Oct 1, 2007

Research paper thumbnail of Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal

Molecular Pharmacology

Administration of the allylbarbiturate secobarbital (SB) to phenobarbital-pretreated rats is know... more Administration of the allylbarbiturate secobarbital (SB) to phenobarbital-pretreated rats is known to result in structural and functional loss of hepatic cytochrome P-450 and generation of N-alkylated prosthetic heme derivatives. Isozyme-selective functional markers have led us to confirm P-450b as the isozyme selectively inactivated by the drug. In contrast to its inactivation by allylisopropylacetamide, such SB-inactivated P-450b is not amenable to structural and functional repair by exogenous heme, for reasons that remain unclear. In an effort to gain some insight, we have explored various possible mechanisms. In the course of these studies with rat liver microsomes enriched in P-450b as well as isolated purified P-450b, we have found that, along with prosthetic heme alkylation, a significant fraction of the hemoprotein also undergoes drug-mediated alkylation of the apocytochrome, presumably at the active site. Accordingly, an equimolar ratio of irreversibly bound drug to functio...

Research paper thumbnail of Solid-phase extraction protocol for isolating retinol-d4 and retinol from plasma for parallel processing for epidemiological studies

Clinical Chemistry

Solid-phase extraction permits the parallel processing of samples in large numbers. We have appli... more Solid-phase extraction permits the parallel processing of samples in large numbers. We have applied this technique to the isolation of retinol isotopomers from plasma of humans participating in a study of vitamin A stable isotope dilution. The isotopomers were analyzed by gas chromatography/mass spectrometry. The extraction involves the separation of retinol from its aqueous matrix with a C18 silica-based sorbent followed by removal of lipid contaminants with an aminopropyl silica-based sorbent. Overall recovery of retinol from plasma was 47.2% +/- 1.8%. Purity of the retinol isolated from plasma is comparable with that obtained with a single HPLC method. This method permits the preparation of 32 samples per day by one analyst. Elimination of the need for HPLC permits sample preparation in the field with a minimum of equipment and technical skill.

Research paper thumbnail of Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils

PloS one, 2015

Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (... more Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever) in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis) as well as upon contact (by serum-dependent adhesion and phagocytosis). This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under ...

Research paper thumbnail of Identification, molecular characterization, and expression analysis of a DOMON-like type 9 carbohydrate-binding module domain-containing protein of Coccidioides posadasii

Medical mycology, 2014

Previously, we investigated the effect of N-acetylglucosamine (GlcNAc) on Coccidioides posadasii ... more Previously, we investigated the effect of N-acetylglucosamine (GlcNAc) on Coccidioides posadasii chitinolytic enzymes during in vitro spherule-endospore (S/E) phase culture. During those studies, sodium dodecyl sulfatepolyacrylamide gel electrophoresis analysis of supernatants from S/E phase cultures grown in Converse medium with or without added GlcNAc revealed a ∼ 28-kDa band (CFP28), whose abundance was increased by GlcNAc in parallel with the chitinolytic enzymes. Mass spectrometry (MS) of the CFP28 band revealed peptides that matched an open reading frame found in the tentative consensus sequence, TC20325, retrieved from the Dana Farber Cancer Institute C. posadasii Gene Index Database. The TC20325 cDNA sequence was used to design internal primers based on MS peptides and a full-length cDNA was isolated using a combination of rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. The deduced amino acid sequence of the full-length cDNA consists of ...

Research paper thumbnail of The active sites of cytochromes P450 IA1, IIB1, IIB2, and IIE1. Topological analysis by in situ rearrangement of phenyl-iron complexes

The Journal of biological chemistry, Jan 15, 1991

The reactions of cytochromes P450 IA1, IIB1, IIB2, and IIE1 with phenyldiazene yield complexes wi... more The reactions of cytochromes P450 IA1, IIB1, IIB2, and IIE1 with phenyldiazene yield complexes with absorption maxima at either 474 or 480 nm. Anaerobic extraction of the prosthetic group from the phenyldiazene-treated proteins followed by its exposure to oxygen and strong acid produces an equal mixture of the four possible N-phenylprotoporphyrin IX regioisomers. Exposure of the anaerobically extracted heme complexes to oxygen in the absence of strong acid results in their decomposition to heme and products other than N-phenylprotoporphyrin IX. These results show that the 474/480 nm absorption maxima are due to sigma phenyl-iron complexes. Treatment of the intact hepatic cytochrome P450 complexes with K3Fe(CN)6 results in disappearance of the 474/480 nm band. Extraction of the prosthetic group then yields only the two N-phenylprotoporphyrin IX regioisomers with the N-phenyl group on pyrrole rings A and D. The same regioisomer pattern is obtained if the cytochrome P450IA1 phenyl-iron...

Research paper thumbnail of Latency-Associated Sense Transcripts Are Expressed during in Vitro Human Cytomegalovirus Productive Infection

Virology, 2000

Published studies have identified novel sense transcripts in latent human cytomegalovirus (HCMV) ... more Published studies have identified novel sense transcripts in latent human cytomegalovirus (HCMV) infection. These cytomegalovirus latency-associated transcripts (CLTs) have start sites upstream from the MIE gene productive start site (PSS). We evaluated the expression of the sense CLTs in an in vitro HCMV productive infection. Transcripts with initiation sites upstream from the PSS were detected in infected human fibroblasts using reverse transcription-polymerase chain reaction and 5' rapid amplification of cDNA ends (RACE) analysis. DNA sequencing of 5' RACE PCR products confirmed that the start sites were consistent with sense CLT expression. Furthermore, ribonuclease protection assay analysis showed that transcripts initiating at the latent start site-1 were most abundant at late times postinfection after transcription from the PSS had decreased. In addition, transcription consistent with sense CLT expression was identified in HCMV-infected dTHP-1 cells, monocyte-derived macrophages, and endothelial cells, as well as in clinical isolate-infected human fibroblasts. These findings clearly demonstrate the expression of sense CLTs during in vitro HCMV infection.

Research paper thumbnail of Molecular cloning, characterization and expression analysis of two β-N-acetylhexosaminidase homologs of Coccidioides posadasii

Research paper thumbnail of Racial Differences in Clinically Localized Prostate Cancers of Black and White Men

The Journal of Urology, 1998

Purpose: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression... more Purpose: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences.

Research paper thumbnail of Early Treatment With Fluconazole May Abrogate the Development of IgG Antibodies in Coccidioidomycosis

Clinical Infectious Diseases, 2011

Background. We have observed a number of patients who fail to develop coccidioidal complement fix... more Background. We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease.

Research paper thumbnail of Drug-Induced Modulations of Hepatic Heme Metabolism Neurological Consequences

Annals of the New York Academy of Sciences, 1987

Research paper thumbnail of Molecular Cloning and Expression of a cDNA Encoding a Coccidioides posadasii Cu,Zn Superoxide Dismutase Identified by Proteomic Analysis of the Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, 2007

Research paper thumbnail of Characteristics of the Protective Subcellular Coccidioidal T27K Vaccine

Annals of the New York Academy of Sciences, 2007

While the whole killed spherule vaccine, protective in mice and monkeys, did not prevent coccidio... more While the whole killed spherule vaccine, protective in mice and monkeys, did not prevent coccidioidal disease in humans, the 27K vaccine, a soluble derivative, retains protective activity in mice with little irritant action. Gel filtration and anion exchange fractions of thimerosal-inactivated spherules (T27K), when administered with alum adjuvant, also protect mice against lethal respiratory coccidioidal challenge. However, the superb protection afforded by T27K antigens is maintained for some 3 months, but may then diminish. This appears unrelated to the aging of the mice. Prolongation of the protective action may require addition of a different adjuvant or administration of booster doses of vaccine.

Research paper thumbnail of Method for the Simultaneous Determination of Retinol and β-Carotene Concentrations in Human Tissues and Plasma

Analytical Biochemistry, 2002

To understand differential tissue distribution of retinoids and carotenoids, as it might influenc... more To understand differential tissue distribution of retinoids and carotenoids, as it might influence biological processes in humans, we developed and demonstrated a method for measuring them in selected human tissues. The method includes internal standards and a secondary reference standard to eliminate the need for external standard calibration and to minimize sample-handling errors. Tissues were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were extracted with organic solvent containing internal standards. Analytes were separated using isocratic liquid chromatography and quantified at 325 nm for retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t-butyloxime served as internal standards. Plasma, breast, and fat from breast surgery patients and colon, liver, muscle, and fat from colon surgery patients were analyzed. Within-day relative standard deviations (RSDs) for plasma were <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for beta-carotene and <0.04 for retinol. Saponification ensured complete extraction of retinol and beta-carotene and removal of triglycerides that "foul" chromatographic columns. It seems retinol and beta-carotene concentrations in tissues and blood of cancer patients are the same or higher than those in corresponding tissues of patients without these cancers.

Research paper thumbnail of Identification, Molecular Characterization and Evaluation of Some Ruminal Bacteria That Catalyze and Degrade Plant Cellulosic Materials

American Journal of Applied Sciences, 2014

Research paper thumbnail of Behavioral and neurochemical changes in folate-deficient mice

Physiology & Behavior, 1995

changes in folate-deficient mice. PHYSIOL BEHAV 58(5) 935-941, 1995.--Weanling mice were fed an a... more changes in folate-deficient mice. PHYSIOL BEHAV 58(5) 935-941, 1995.--Weanling mice were fed an amino acid-based diet supplemented with 0 or 11.3 /.~mol folic acid/kg diet for ~ 38 days to study behavior and neurochemistry in folate deficiency. After ~ 5 wk, mice fed the unsupplemented diet weighed ~ 70% as much those fed the supplemented diet. After 2 wk, mice fed the unsupplemented diet consistently discarded (spilled) more food, and after ~ 5 wk, they had spilled 3 times more than mice fed the supplemented diet. Serum folate, brain folate and brain S-adenosylmethionine of mice fed the unsupplemented diet were 4, 53, and 60% as high, respectively, as those of mice fed the supplemented diet. Pathologic changes were not evident in brain, spinal cord, or skeletal muscle of folate-deficient mice. The hypothalamic 5-hydroxyindole acetic acid/serotonin ratio and caudate dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations were lower in deficient than control mice. Folate-deficient mice develop a behavioral activity, food spilling, which may have a neurochemical basis in the serotonin and dopamine systems.