Abstract
Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.
Highlights
Learning and memory are two critical functions of the brain and several different regions within the brain have been demonstrated to have involvement in the consolidation of diverse forms of learning/memory, including the cortex, striatum, amygdala and hippocampus [1]
Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the brain-derived neurotrophic factor (BDNF) levels via a cAMP/Protein kinase A (PKA)/cAMP-responsive element binding (CREB)-dependent pathway
The cortex has involvement with spatial learning; the striatum correlates with motor skills; the amygdala is related to emotional memory; and the hippocampus is involved in spatial learning and working and recognition memory
Summary
Learning and memory are two critical functions of the brain and several different regions within the brain have been demonstrated to have involvement in the consolidation of diverse forms of learning/memory, including the cortex, striatum, amygdala and hippocampus [1]. The cortex has involvement with spatial learning; the striatum correlates with motor skills; the amygdala is related to emotional memory; and the hippocampus is involved in spatial learning and working and recognition memory. Many have generally recognized the hippocampus as the most critical region [2,3]. Among the NTs, the brain-derived neurotrophic factor (BDNF) in general performs the highest expression in the brain [4]. Activation of the cAMP/PKA/cAMP-responsive element binding (CREB) protein signaling pathway can lead to the induction of an array of genes, including BDNF [7]. Phosphodiesterase (PDE) is the Molecules 2020, 25, 3667; doi:10.3390/molecules25163667 www.mdpi.com/journal/molecules
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