Amol Bhandage

Forskare vid Institutionen för medicinsk cellbiologi, Forskargrupp Bryndis Birnir

Husargatan 3
751 23 Uppsala
Box 571
75123 Uppsala

Detta stycke finns inte på svenska, därför visas den engelska versionen.

Detta stycke finns inte på svenska, därför visas den engelska versionen.

Alcoholism and excitatory and inhibitory signalling in the human brain

Glutamate and γ-aminobutyric acid (GABA) are the principal excitatory and inhibitory neurotransmitters in the CNS where they can activate ionotropic glutamate (iGlu - AMPA, kainate and NMDA) and GABA-A receptors, respectively, which are modulated by many types of drugs and substances including alcohol. Using real time quantitative polymerase chain reaction, I have shown that iGlu and/or GABA-A receptor subunits were expressed in the hippocampus dentate gyrus (HDG), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), central amygdala (CeA), caudate and putamen of the human brain and their expression was altered by chronic excessive alcohol consumption (Jin et al., 2014a, 2014b; Bhandage et al., 2014). It indicates that excitatory and inhibitory neurotransmission may have been altered in the brain of human alcoholics. It is possible that changes in one type of neurotransmitter system may drive changes in another. These brain regions also play a role in brain reward system. Any changes in them may lead to changes in the normal brain functions.

Neurotransmitter signalling in immune cells and effects of physiological and pathological conditions

Apart from the CNS, neurotransmitters - glutamate and GABA are also present in the blood and can be synthesized by immune cells. They may act as immunomodulators of circulating immune cells and can affect immune function through glutamate and GABA receptors. My research is focused on functional characterization of neurotransmitter receptors i.e. GABA-A and ionotropic glutamate receptors in immune cells, more specifically in T cells. I found that T cells from human, rat and mouse lymph nodes expressed the mRNAs and proteins for specific GABA-A receptor subunits. GABA-evoked transient and tonic currents recorded using the patch clamp technique demonstrate the functional GABA-A channel in T cells (Mendu et al., 2012). Furthermore, the mRNAs for specific iGlu, GABA-A and GABA-B receptor subunits and chloride cotransporters were detected in peripheral blood mononuclear cells (PBMCs) from men, non-pregnant women, healthy and depressed pregnant women (Bhandage et al., 2015, 2016). The results indicate that the expression of iGlu, GABA-A and GABA-B receptors is related to gender, pregnancy and mental health and support the notion that glutamate and GABA receptors may modulate immune function. Intra- and interspecies variability exists in the expression and it is further influenced by physiological conditions. Apart from this, I have characterized expression of calcium channels – VGCCs and CRACs in these immune cells (Unpublished data).

T1D: I have studied immunological aspects of T1D in relation to neurotransmitter signalling. I have studied expression of ion channels – GABA-A, AMPA, NMDA, Kainate, VGCC, CRAC; GABA-B receptors, chloride transporters, GABAergic system (GAT, GAD, GABA-T and other molecules) in T1D immune cells and found very interesting results. Several of these molecules were altered in T1D immune cells. Functionally, GABA has inhibited the proliferation and cytokine secretion profile of T1D immune cells (Unpublished data)

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Amol Bhandage
Senast uppdaterad: 2021-03-09