Executive Summary : | The memory processing and consolidation in the adult brain are done through neuronal plasticity and adult hippocampal neurogenesis. The neural plasticity is established by the appearance of dendritic spines and increased arbors. The hippocampal neurons exhibit dendritic spines that form the important sites for excitatory synaptic contact. BDNF gene expression is regulated by Cyclic adenosine monophosphate Response Element-Binding protein (CREB) (Yi et al., 2015). The CREB acts as an important transcription factor in hippocampal neurons and plays a crucial role in adult neurogenesis, neuronal survival, and synaptic plasticity. In addition, the increased CREB phosphorylation upregulates protein kinase A (PKA), including BDNF and other proteins required for synaptic and neuronal plasticity (Yi et al., 2015). Besides, Mitogen-activated protein kinases (MAPKs) induce synaptic plasticity and influence memory function (Abdul Rahman et al., 2016). Furthermore, the c-Raf serine/threonine kinases activate the extracellular signal-regulated kinases (ERKs). Also, the c-Raf activated MAPK-ERK kinase (MEK) stimulates the ERK1/2 pathway to regulate neural gene expression associated with synaptogenesis (Giachello et al.,2010). Thus, c-Raf/MEK/ERK pathway plays a crucial role in hippocampal memory acquisition (Peng et al., 2010; Sun et al., 2017;). These key pathways, controlling the synaptic plasticity, have been illuminated recently in the normal adult hippocampus in relation to testosterone (Shin et al., 2019). However, no study has been reported on the influence of testosterone on these pathways in the aging hippocampus, especially in relation to the gene regulation during spine morphogenesis. Therefore, the objective of the present study is to delineate the potential role of testosterone on the PKA-CREB-BDNF and the c-Raf/MEK/ERK signaling in regulating postsynaptic density proteins, scaffolding proteins and, pre and postsynaptic cell adhesion molecules during dendritic spine morphogenesis in hippocampal neurons. Ultimately, to explore the relationship between learning and memory functions through behavioural analysis. The study will be carried out using testosterone-depleted (by castration) young and aged animals. |