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Papers by Jessica Malberg

Journal of psychiatry & neuroscience : JPN, 2004

In the dentate gyrus of the hippocampus, cell birth and maturation into neurons, or neurogenesis,... more In the dentate gyrus of the hippocampus, cell birth and maturation into neurons, or neurogenesis, occur throughout the lifetime of animals and humans. Multiple factors have been shown to regulate adult neurogenesis, and a number of findings in this field have had a large impact on basic and clinical research in depression. It has been reported that both physical and psychosocial stress paradigms, as well as some animal models of depression, produce a decrease in hippocampal cell proliferation and neurogenesis. Conversely, long-term, but not short-term, treatment with different classes of antidepressant drug increases cell proliferation and neurogenesis. Patients with depressive disorders or post-traumatic stress disorder have reduced hippocampal volume. Given this interaction of stress, depression and neurogenesis, a current hypothesis is that reduced adult hippocampal cell proliferation or neurogenesis may be involved in the pathophysiology of depression and that reversal or preven...

Neuropsychopharmacology, 2003

Behavioural Pharmacology, 1999

Psychopharmacology, 2007

Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the anti... more Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs.

The substituted amphetamine 3,4-methylenedioxymetham-phetamine (MDMA) has been shown to be neurot... more The substituted amphetamine 3,4-methylenedioxymetham-phetamine (MDMA) has been shown to be neurotoxic to sero-tonin (5HT) terminals in the rat, and rat body temperature (TEMP) has been shown to affect this neurotoxicity. This study looked at the effect on CORE TEMP of three drugs that protect against MDMA neurotoxicity in the rat. Male Holtzmann rats were injected with a control saline (SAL) injection or with ket-anserin (KET; 6 mg/kg), a-methyl-p-tyrosine (AMPT; 75 mg/kg) or fluoxetine (FLUOX; 1 0 mg/kg) before a 40-mg/kg MDMA or SAL injection. CORE TEMP was recorded throughout the study using a noninvasive pentoneally implanted temperature probe. Rats pretreated with KET had no change in CORE TEMP until MDMA was injected, at which time an immediate hypothermia was seen that continued for 1 80 minutes, with a peak low of

Studies at the basic and clinical levels demonstrate that neuronal atrophy and cell death occur i... more Studies at the basic and clinical levels demonstrate that neuronal atrophy and cell death occur in response to stress and in the brains of depressed patients. Although the mechanisms have yet to be fully elucidated, progress has been made in characterizing the signal transduction cas-cades that control neuronal atrophy and programmed cell death and that may be involved in the action of antide-pressant treatment. These pathways include the cyclic adenosine monophosphate and neurotrophic factor signal transduction cascades. It is notable that these same pathways have been demonstrated to play a pivotal role in cellular models of neural plasticity. This overlap of plasticity and cell survival pathways, together with studies demonstrating that neuronal activity enhances cell sur-vival, suggests that neuronal atrophy and death could result from a disruption of the mechanisms underlying neural plasticity. The role of these pathways and failure of neuronal plasticity in stress-related mood...

Neurogenesis continues to occur in the adult hippocampus, although many of the newborn cells dege... more Neurogenesis continues to occur in the adult hippocampus, although many of the newborn cells degenerate 1–2 weeks after birth. The number and survival of newborn cells are regulated by a variety of environmental stimuli, but very little is known about the intracellular signal transduction pathways that control adult neurogenesis. In the present study, we examine the expression of the phosphorylated cAMP response elementbinding protein (pCREB) in immature neurons in adult hippocampus and the role of the cAMP cascade in the survival of new neurons. The results demonstrate that virtually all immature neurons, identified by triple immunohistochemistry for bromodeoxyuridine (BrdU) and polysialic acid-neural cell adhesion molecule (PSA-NCAM), are also positive for pCREB. In addition, upregulation of cAMP (via pharmacological inhibition of cAMP breakdown or by antidepressant treatment) increases

Biological Psychiatry

Of Duman's many influential findings, the finding that long-term treatment with antidepressan... more Of Duman's many influential findings, the finding that long-term treatment with antidepressant drugs produces an increase in neurogenesis in the subgranular zone of the adult hippocampus may be one of the most enduring and far-reaching. This novel discovery and his decades of continued research in the field led to a new hypothesis about the mechanism of action of antidepressants, providing a critical step in our understanding of the neurotrophic hypothesis of depression and synaptic plasticity. It is now accepted that antidepressant treatments can oppose and even reverse the effects of stress on the brain and on newly born hippocampal cells, possibly via neurotrophic factors, which Duman had continued to explore. Furthermore, ablation studies have shown preclinically that hippocampal neurogenesis may be necessary for some of the clinical effects of antidepressant drugs. Duman's laboratory continued to interrogate neurotrophins and synaptic plasticity, demonstrating that newer clinically approved antidepressant compounds also affect neurogenesis and synaptic plasticity. In this review, we summarize Duman's original findings and discuss the current state of the field of neurogenesis with respect to animal models and human studies and the implications of those findings on the field of drug discovery.

The Faseb Journal, Mar 1, 2006

The present invention relates to 2-oxo-2,3 of formula I - indole, or a pharmaceutically acceptabl... more The present invention relates to 2-oxo-2,3 of formula I - indole, or a pharmaceutically acceptable salt, racemic mixture, or their corresponding enantiomers and / or optical isomers and / or stereoisomers that It relates: Wherein (N (N R n is 1 or 2; When n is 2, R R R R m is 1 or 2; if m is 2, R

Journal of Pharmacology and Experimental Therapeutics, Nov 1, 2001

Proliferation and maturation of neurons has been demonstrated to occur at a significant rate in d... more Proliferation and maturation of neurons has been demonstrated to occur at a significant rate in discrete regions of adult brain, including the hippocampus and subventricular zone. Moreover, adult neurogenesis is an extremely dynamic process that is regulated in both a positive and negative manner by neuronal activity and environmental factors. It has been suggested to play a role in several important neuronal functions, including learning, memory, and response to novelty. In addition, exposure to psychotropic drugs or stress regulates the rate of neurogenesis in adult brain, suggesting a possible role for neurogenesis in the pathophysiology and treatment of neurobiological illnesses such as depression, post-traumatic stress disorder, and drug abuse. As the mechanisms that control adult neurogenesis continue to be identified, the exciting prospect of developing pharmacological agents that specifically regulate the proliferation and maturation of neurons in the adult brain could be fulfilled.

Journal of psychiatry & neuroscience: JPN

ABSTRACT

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience