Increase of cannabinoid CB1 receptor density in the hippocampus of streptozotocin-induced diabetic rats

Abstract

In the hippocampus, impaired neurophysiology, compromised neurogenesis, and eventually apoptosis accompany cognitive deficits in insulinopenic (type-1) diabetes (T1D). The underlying pathological mechanisms remain to be defined. The hippocampus has a high density of the cannabinoid type 1 receptor (CB 1 R), which has been shown to control several brain functions affected by diabetes, such as synaptic plasticity, glucose utilisation, memory consolidation and cognition, and maturation and survival of hippocampal neurons. However, the role of this receptor has not been investigated yet in diabetic encephalopathy. We report now that in the streptozotocin animal model of T1D, the hippocampal densities of CB 1 R protein and of specific CB 1 R binding sites are significantly increased both in the nerve terminals and in total membranes (changes between 13% and 38%), whereas CB 1 R mRNA expression is decreased by 25%, suggesting that CB 1 Rs might play a role in diabetic encephalopathy.

Cannabinoid receptor 1 mediates high glucose-induced apoptosis via endoplasmic reticulum stress in primary cultured rat mesangial cells

“…Endocannabinoids may control energy metabolism via CB 1 R. Recent evidence demonstrates that CB 1 R antagonists have beneficial effects in obese patients with type 2 diabetes (55). In addition, the hippocampal densities of CB 1 R protein and specific CB 1 R binding sites are significantly increased in the animal model of streptozotocin-induced type 1 diabetes (13). Our recent report also demonstrated that palmitic acid induces CB 1 R activation in proximal tubule cells, suggesting that hyperlipidemia increases CB 1 R activation, which may be associated with the onset of diabetic nephropathy (28).…”

Expression of Cannabinoid CB1 Receptors in Models of Diabetic Neuropathy

“…In the present study, CB 1 receptor protein appears to be down-regulated in nerve cells grown in conditions mimicking hyperglycemia and in neurons from diabetic rats. A study recently published by Duarte et al (2007) revealed decreased CB 1 mRNA expression in the hippocampus of diabetic rats, concomitant with an increase in CB 1 protein density. Although the mRNA data are in agreement with our findings, differences in neuronal CB 1 protein expression between hippocampus (increased in Duarte et al, 2007) and DRG (decreased in the present study) from STZinduced diabetic rats may reflect site-specific signaling pathways involved in mRNA translation, e.g., activation of the key rate-limiting translational pathway mammalian target of rapamycin in hippocampal neurons (Duarte et al, 2007).…”

Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice

“…Mounting evidences show that hippocampus and frontal cortex are involved in spatial learning and memory [39][40][41]. In our previous experiments, we employed Cresyl Violet staining to detect the survival of neurons in hippocampal and frontal cortex regions to study the effect of astaxanthin treatment on neurons in DE mice.…”

“…In addition, treatment with astaxanthin could significantly improve impaired performance of learning and memory in the DE+AST group compared to the DE group. Our findings demonstrated that astaxanthin could prevent cognitive impairments induced by hyperglycemia in DE mice.Furthermore, astaxanthin treatment has no effect on normal mice, which was shown by the N+AST group.Mounting evidences show that hippocampus and frontal cortex are involved in spatial learning and memory [39][40][41]. In our previous experiments, we employed Cresyl Violet staining to detect the survival of neurons in hippocampal and frontal cortex regions to study the effect of astaxanthin treatment on neurons in DE mice.…”