ABSTRACT
An involvement of one particular neurotrophin, namely, the brain-derived neurotrophic factor (BDNF), has been demonstrated in the pathophysiology Huntington's disease. Type-1 cannabinoid (CB1) receptor has been postulated to upregulate BDNF gene transcription. To better understand the relationship between CB1 and BDNF levels in a situation where the striatum is degenerating, we studied, by dual label immunofluorescence, the distribution of CB1 and BDNF in cortical neurons projecting to the striatum in our rat quinolinic acid model of striatal excitotoxicity. We completed our study with quantitative analyses of BDNF protein levels and CB1 binding activity in the cortex. We show that, 2 weeks post lesion, cortical neurons contain more BDNF compared with controls and to earlier time points. Such BDNF up-regulation coincides with a higher binding activity and an increased protein expression of CB1. We suggest that after excitotoxic lesions, CB1 might, at least transiently, upregulate BDNF in the attempt to rescue striatal neurons from degeneration.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/metabolism , Corpus Striatum/metabolism , Receptor, Cannabinoid, CB1/metabolism , Animals , Cell Communication/physiology , Cell Survival/physiology , Cerebral Cortex/physiopathology , Corpus Striatum/drug effects , Corpus Striatum/physiopathology , Cytoprotection/physiology , Disease Models, Animal , Fluorescent Antibody Technique , Huntington Disease/metabolism , Huntington Disease/physiopathology , Male , Nerve Degeneration/chemically induced , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Neurotoxins , Protein Binding , Quinolinic Acid , Rats , Rats, Wistar , Time Factors , Up-Regulation/physiologyABSTRACT
Several lines of evidence indicate that cannabinoids, among other functions, are involved in motor control. Although cannabinoid receptors (CB(1)) mRNA has been observed in medium-sized spiny neurons of the striatum, a description of the precise localization of CB(1) at a protein level among striatal cells is still lacking. Therefore, we performed immunohistochemical studies with light and confocal microscopy to identify neuronal subpopulations that express CB(1) and to assess the distribution of the receptor within these neurons. In our single label light microscopy study, CB(1) was observed in most medium-sized neurons of the caudate-putamen. However, CB(1) was also present in large-sized neurons scattered throughout the striatum. Our dual-label study showed that 89.3% of projection neurons in matrix contain CB(1), and that 56.4% of projection neurons in patch are labeled for CB(1). To investigate the presence of CB(1) among the different subclasses of striatal interneurons we performed a double-labeling study matching CB(1) and each of the striatal interneuron markers, namely, choline acetyl-transferase, parvalbumin, calretinin, and nitric oxide synthase. Our double-label study showed that most parvalbumin immunoreactive interneurons (86.5%), more than one-third (39.2%) of cholinergic interneurons, and about one-third (30.4%) of the NOS-positive neurons are labeled for CB(1). Calretinin-immunolabeled neurons were devoid of CB(1).