Streptozotocin induced hyperglycemia stimulates molecular signaling that promotes cell cycle reentry in mouse hippocampus.

AIMS: Cerebral atrophy resulting from neurodegeneration is highly prevalent in individuals with diabetes; however, the underlying mechanisms for diabetic neurodegeneration are not fully understood. Here we hypothesized that hyperglycemia induces molecular signaling that favors induction of proliferation in post mitotic, fully differentiated hippocampal neurons. MATERIALS AND METHODS: Streptozotocin (150 mg/kg) was intraperitoneally injected to four months old male mice to induce diabetes. Hippocampal tissue was subjected to molecular analysis of wingless-related integration site, extracellular signal regulated kinase, and brain derived neurotrophic factor signaling, and cell cycle regulation. KEY FINDINGS: Hyperglycemia did not alter wingless-related integration site signaling or cyclin E levels in the hippocampus. There were reductions in extracellular signal regulated kinase activation and brain derived neurotrophic factor levels along with elevated cyclin D1 levels. SIGNIFICANCE: These findings indicate that hyperglycemic conditions can stimulate cell cycle progression in the hippocampus in vivo. These new insights into the disease mechanisms could support the development of novel therapeutics aimed to provide neuroprotection in diabetic patients.

Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1ß protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus.