Recalibrating the Existence of New Neurons in Adult Brain (original) (raw)

Human Adult Neurogenesis: Evidence and Remaining Questions

Cell stem cell, 2018

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.

Adult neurogenesis and Alzheimer's disease

Science

Until recently, progressive neurodegenerative diseases such as Parkinson's or Alzheimer's disease (AD), as well as acute brain injuries like stroke were thought to result in an irreversible loss of neurons with no possibility of neuronal regeneration. In the last few years, this belief has been challenged by numerous studies that have demonstrated that specialized areas of the brain retain pluripotent precursors with the capacity to regenerate neurons in adult mammals such as rodents1-3, nonhuman primates4, and humans5,6. The function of neurogenesis in the adult brain is still unknown, and we are far from understanding the processes regulating it. The available knowledge indicates that significant limitations at all key steps in the process will have to be overcome to achieve functionally relevant replacement of lost brain networks from endogenous neuronal stem cells. However, that new neurons are added continously to the adult brain is a discovery that has already changed the way we think about neurobiology and may soon change the way we understand and approach neurodegenerative diseases.

Adult neurogenesis, human after all (again): Classic, optimized, and future approaches

Behavioural Brain Research, 2019

In this perspective article, we reflect on the recent debate about the existence of human neurogenesis and discuss direct, and also indirect, support for the ongoing formation, and functional relevance, of new neurons in the adult and aged human hippocampus. To explain the discrepancies between several prominently published human studies, we discuss critical methodological aspects and highlight the importance of optimal tissue preservation and processing for histological examination. We further discuss novel approaches, like single-cell/nucleus sequencing and magnetic resonance spectroscopy, that will help advance the study of human neurogenesis to its fullest potential-understanding its contribution to human hippocampal functions and related disorders like depression and dementia.

Human Hippocampal Neurogenesis Persists throughout Aging

Cell stem cell, 2018

Adult hippocampal neurogenesis declines in aging rodents and primates. Aging humans are thought to exhibit waning neurogenesis and exercise-induced angiogenesis, with a resulting volumetric decrease in the neurogenic hippocampal dentate gyrus (DG) region, although concurrent changes in these parameters are not well studied. Here we assessed whole autopsy hippocampi from healthy human individuals ranging from 14 to 79 years of age. We found similar numbers of intermediate neural progenitors and thousands of immature neurons in the DG, comparable numbers of glia and mature granule neurons, and equivalent DG volume across ages. Nevertheless, older individuals have less angiogenesis and neuroplasticity and a smaller quiescent progenitor pool in anterior-mid DG, with no changes in posterior DG. Thus, healthy older subjects without cognitive impairment, neuropsychiatric disease, or treatment display preserved neurogenesis. It is possible that ongoing hippocampal neurogenesis sustains huma...

Hippocampal neurogenesis during normal and pathological aging

Psychoneuroendocrinology, 2007

It is now widely accepted that new neurons continue to be added to the brain throughout life including during normal aging. The finding of adult neurogenesis in the hippocampus, a structure involved in the processing of memories, has favored the idea that newborn neurons might subserve cognitive functions. Recent work on human post-mortem tissues and mice models of Alzheimer's disease (AD) has reported persistent hippocampal proliferative capacity during pathological aging. Although it is not yet clear whether neurogenesis leads to the production of fully functional mature neurons in AD brains, these findings open prospects for cell-replacement therapies. Strategies aimed at promoting neurogenesis may also contribute to improve cognitive deficits caused by normal or pathological aging.

Neurogenesis in Alzheimer's disease

Journal of anatomy, 2011

It is widely acknowledged that neural stem cells generate new neurons through the process of neurogenesis in the adult brain. In mammals, adult neurogenesis occurs in two areas of the CNS: the subventricular zone and the subgranular zone of the dentate gyrus of the hippocampus. The newly generated cells display neuronal morphology, generate action potentials and receive functional synaptic inputs, their properties being equivalent to those of mature neurons. Alzheimer’s disease (AD) is the widespread cause of dementia, and is an age-related, progressive and irreversible neurodegenerative disease that results in massive neuronal death and deterioration of cognitive functions. Here, we overview the relations between adult neurogenesis and AD, and try to analyse the controversies in the field. We also summarise recent data obtained in the triple transgenic model of AD that show time- and region-specific impairment of neurogenesis, which may account for the early changes in synaptic plasticity and cognitive impairments that develop prior to gross neurodegenerative alterations and that could underlie new rescue therapies.

Dynamics of Hippocampal Neurogenesis in Adult Humans

SUMMARY Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived 14 C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hip-pocampal neurons constituting one-third of the neu-rons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neu-rons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neuro-genesis may contribute to human brain function.

The dynamics of adult neurogenesis in human hippocampus

Neural Regeneration Research, 2016

The dynamics of adult neurogenesis in human hippocampus Historical Perspective The inability of the adult brain to generate neurons throughout life was a central dogma in neurobiology. For decades, there was little or no progress for the field. The adult brain was thought to be hard wired and incapable of generating new neurons. A famous neurobiologist, Santiago Ramon y Cajal in 1913 stated "In the adult centres, the nerve paths are something fixed, ended and immutable. Everything may die, nothing may be regenerated, " (Ramon y Cajal, 1928). And this was in part a reason for slow progress for decades for the field. The complexity of the neural networks in an adult brain affirmed this view, hence new neurons were assumed if added would destabilize the neuronal network (Jessberger and Gage, 2014) as such, it was impossible to integrate the new cells. Incorporation of new neurons was thought that it would destabilize

Neurogenesis in Human Hippocampus: Implications for Alzheimer Disease Pathogenesis

Neuroembryology and Aging, 2006

Alzheimer disease (AD) is the most common cause of dementia, and its prevalence is directly related to age . Moreover, the increasing life expectancy, rising from 50 years at the beginning of the last century to approximately 80 years today, inevitably brings a higher incidence of age-related illnesses, including AD, resulting in an increase from 4 million individuals currently affected with AD in the United States to an estimated 14 million by 2050 . In spite of these figures, the lack of progress toward effective therapy is striking.

Adult hippocampal neurogenesis and aging

European Archives of Psychiatry and Clinical Neuroscience, 2007

The demographic changes in the foreseeable future stress the need for research on successful cognitive aging. Advancing age constitutes a primary risk factor for disease of the central nervous system most notably neurodegenerative disorders. The hippocampus is one of the brain regions that is prominently affected by neurodegeneration and functional decline even in what is still considered "normal aging". Plasticity is the basis for how the brain adapts to changes over time. The discovery of adult hippocampal neurogenesis has added a whole new dimension to research on structural plasticity in the adult and aging hippocampus. In this article, we briefly summarize and discuss recent findings on the regulation of adult neurogenesis with relevance to aging. Aging is an important co-variable for many regulatory mechanisms affecting adult neurogenesis but so far, only few studies have specifically addressed this interaction. We hypothesize that adult neurogenesis contributes to a neural reserve, i.e. the maintained potential for structural plasticity that allows compensation in situations of functional losses with aging. As such we propose that adult neurogenesis might contribute to the structural correlates of successful aging.