Stress and adult Neurogenesis

Adult neurogenesis, the addition of new neurons in certain areas of the adult brain such as the dentate gyrus of the hippocampus and olfactory bulb has been well documented. However the functional significance of this process still remains unclear. Studies from our lab have shown that chronic restraint stress leads to cognitive deficits associated with morphological and biochemical alterations. Following this, they have also shown exposure to enriched environment or administration of the pharmacological agents to be ameliorative of the stress-induced deficits. Consequently, spatial learning and long-term potentiation (LTP) affected following stress was also restored by the reversal paradigms. Neurogenesis is regulated by various factors, both internal and external. Various forms of chronic stress are shown to decrease the neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Our current results are also in accordance with these studies, showing that chronic restraint stress decreases hippocampal neurogenesis. Further, we have also evaluated the changes in neurogenesis following the reversal paradigms. Interestingly, the stress-induced decrease in neurogenesis is restored by exposure to short term enrichment and by treatment with either bromocriptine (dopaminergic D2 receptor agonist) or oxotremorine (muscarinic agonist). 

Our results show that the reversal strategies are favourable to neurogenesis, a process closely associated with learning. This might underlie alterations in several factors including elevated trophic factor production, angiogenesis, and alterations in the neurotransmitter levels. However, exploring the possibility that these new cells may mediate increased synaptic plasticity and improved learning is an attractive one. It is interesting to determine whether such factors induce the reversal stragies’-enhanced synaptic plasticity and learning independently, or act indirectly, supporting survival and connectivity of newborn neurons. This could add significantly to the functional significance to adult neurogenesis, a process conserved through evolution across a wide range of species including mammals.

Representative images of the newly formed cells in the hippocampus labelled using BrdU-immunohistochemistry.  Stress (B) significantly decreased the number of newly formed cells compared to Normal control (A). Short term enrichment to stressed animals completely restored the stress-induced decrease in proliferation (D). Per se enrichment (C) increased the proliferation in hippocampus. Scale bar in B = 10µm and applies to all frames and the scale bar in the inset of A = 20µm. Also see Veena et al., Journal of Neuroscience Research 2008.