Magic™ Anti-CaMK II (Phospho T286) polyclonal antibody

The mesolimbic dopamine system is important for reward-oriented behaviours, such as drinking and eating. However, the precise involvement of dopaminergic neurons and dopamine receptors in water drinking behaviour remains unclear. Here, we generated triple transgenic mice harbouring Slc6a3(DAT)-icre/ERT2, Camk2a-loxP-STOP-loxP-tetracycline transactivator and tetO-tetanus toxin constructs, in which the release of dopamine is blocked by tetanus toxin. These mice, referred to as dopamine secretion interference mice, had reduced dopamine secretion in the striatum (61.4%) and the nucleus accumbens (54.5%). They showed adequate limb strength and food consumption, similarly to control mice, but exhibited motor control impairment in a challenging rotarod test. Dopamine secretion interference mice made fewer licks and had fewer bursts than control mice during a licking test under thirsty conditions. To elucidate the influence of dopamine receptors in the altered drinking behaviour, a dopamine D1 or D2/D3 receptor agonist (A68930 or ropinirole, respectively) was administered prior to the licking microstructure analysis. Treatment with the D1 agonist restored the total number of licks but not the burst number in dopamine secretion interference mice. By contrast, the D2/3 agonist impeded water drinking behaviour in both transgenic and control mice. The present findings indicate that D1 receptor activation partially ameliorates the altered drinking behaviour of the dopamine secretion interference mice and suggest that D1 receptor activity impacts drinking under thirsty conditions.

We previously showed that treatment with lanthionine ketimine ethyl ester (LKE) reduced disease severity and axonal damage in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis and increased neuronal maturation and survival in vitro. A major target of LKE is collapsin response mediator protein 2 (CRMP2), suggesting this protein may mediate LKE actions. We now show that conditional knockout of CRMP2 from neurons using a CamK2a promoter to drive Cre recombinase expression reduces disease severity in the myelin oligodendrocyte glycoprotein (MOG)(35-55) EAE model, associated with decreased spinal cord axonal damage, and less glial activation in the cerebellum, but not the spinal cord. Immunohistochemical staining and quantitative polymerase chain reaction show CRMP2 depletion from descending motor neurons in the motor cortex, but not from spinal cord neurons, suggesting that the benefits of CRMP2 depletion on EAE may stem from effects on upper motor neurons. In addition, mice in which CRMP2 S522 phosphorylation was prevented by substitution for an alanine residue also showed reduced EAE severity. These results show that modification of CRMP2 expression and phosphorylation can influence the course of EAE and suggests that treatment with CRMP2 modulators such as LKE act in part by reducing CRMP2 S522 phosphorylation.