Memory Cannabinoids & hippocampus neurogenesis

The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

The fMRI images revealed that the prefrontal cortex, which controls the suppression and retrieval of memories processed by the hippocampus, showed abnormal activation in the patients with stress-related disorders compared to the healthy controls. During the memory suppression phase of the test, patients with stress-related disorders showed greater activation in the hippocampus, suggesting that insufficient activation of the prefrontal cortex could be the basis for inadequate suppression of unwanted traumatic memories stored in the hippocampus.

“These data suggest that the mechanism for memory suppression is dysfunctional in patients with stress-related disorders primarily because of an alteration of the prefrontal cortex,” Dr. Agarwal said. “These patients often complain of poor memory, which might in part be attributed to this altered circuitry,” she added.

According to Dr. Agarwal, fMRI is an important tool in understanding the neurobiological basis of psychiatric disorders and in identifying imaging markers to psychiatric disease, helping clinicians target specific parts of the brain for treatment.

For patient-friendly information on fMRI, visit RadiologyInfo.org.

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