Background: MIR137 is implicated in brain development and encodes a microRNA that regulates neuronal 23 maturation and adult neurogenesis. Recently, a common genetic variant within MIR137 showed genome wide 24 evidence of association with schizophrenia, and with altered amygdala activation in those at genetic risk for 25 schizophrenia. Following this evidence, we investigated the effects of MIR137 genotype on neuronal activity 26 during face processing. 27 Methods: By grouping 81 healthy participants as carrier or non-carriers of the MIR137 rs1625579 risk allele 28 associated with schizophrenia, we investigated MIR137's effects on altered cortical response during an fMRI 29 face processing task and altered functional connectivity using the amygdala as a seed region.30 Results: Homozygous carriers of the risk allele were observed to show relatively increased functional connectivity 31 between the right amygdala and frontal regions that play a key role in emotion processing and regulation 32 (e.g. the cingulate and prefrontal cortex).33 Conclusions: Our findings provide the first evidence that the rs1625579 variant affects fronto-amygdala function-34 al connectivity, providing further evidence that MIR137 may contribute to forms of psychosis in which affective 35 symptoms are more prominent.36
• Exercised rats successfully completed challenging spatial task.• Exercised rats showed increase in KCl-stimulated BDNF release from dentate gyrus.• Exercised rats displayed increases in BDNF expression and cell division in dentate gyrus.• Exercised rats displayed activation of BDNF-stimulated signalling cascade.• BDNF injections mimicked effects of exercise on both memory and signalling events.
a r t i c l e i n f o
b s t r a c tExercise-induced improvements in learning are associated with neurotrophic and neurogenic changes in the dentate gyrus, but the intracellular signalling mechanisms that may mediate these improvements remain unknown. In the current study we investigate the effects of one week of forced exercise on spatial memory and analyse in parallel BDNF-stimulated signalling pathways in cells of the dentate gyrus. Additionally, we test whether a single intracerebroventricular (i.c.v.) injection of BDNF can mimic the observed cognitive and signalling changes. Male Wistar rats were assigned to exercised and sedentary groups and tested in a spatial task post-exercise. Tissue from the dentate gyrus was assessed for expression and release of BDNF, and for changes in expression and activation of TrkB, ERK and synapsin-1. In a separate set of experiments, male Wistar rats received a single i.c.v. injection of BDNF and were then tested in the same spatial learning task. Exercised and BDNF-treated (but not control) rats could successfully complete an object displacement task that tests spatial learning. Exercised rats and BDNF-treated rats displayed increases BDNF expression and ERK1 activation, while exercised rats showed increases in cell division, stimulated BDNF release, TrkB activation, and synapsin-1 expression in the dentate gyrus. We conclude that exercise-induced increases in BDNF in the dentate gyrus are sufficient to cause improvements in spatial memory by activating signalling cascades that enhance synaptic transmission in the hippocampus.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.