The present study showed CCR7, CCR8, CCR9 and CCR10 in the normal Swiss mouse hippocampus at both protein and mRNA levels. CCR7, CCR9 and CCR10 were mainly localized in hippocampal principal cells and some interneurons. CCR9 was also found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area. CCR8 was observed in interneurons. Double-labelling immunocytochemistry revealed that most of calbindin (CB)-, calretinin (CR)-and parvalbumin (PV)-immunopositive neurons expressed CCR7-10, except CR-immunopositive cells in which only 10 to 12% expressed CCR8. During and after pilocarpineinduced status epilepticus, progressive changes of each of CCR7, CCR8, CCR9 and CCR10 proteins occurred in different patterns at various time points. Sensitive real-time PCR showed similar change patterns at mRNA level. At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR-and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons. Double labelling of CCR7, CCR8 and CCR9 with glial fibrillary acidic protein (GFAP) at the chronic stage may suggest an induced expression in reactive astrocytes. The present study may, therefore, for the first time, provide evidence that CCR7-10 may be involved in normal hippocampal activity. The demonstration of the progressive changes of CCR7-10 during and after status epilepticus may open a new area to reveal the mechanism of neuronal loss after status epilepticus and of epileptogenesis. Keywords: CCR7-10, epilepsy, hippocampus, status epilepticus. J. Neurochem. (2007) 100, 1072-1088.The chemokine receptor ligand family has been not only well known to be inductively expressed in different cell types in the CNS in animal models of neurological disorders such as autoimmune encephalomyelitis (Ransohoff et al. 1993;Berman et al. 1996), HTLV-I-associated myelopathy (Umehara et al. 1996), trauma (Berman et al. 1996), acquired immunodeficiency syndrome (AIDS) dementia (Nuovo and Alfieri 1996), stroke or ischaemia (Gourmala et al. 1997;Spleiss et al. 1998), demyelinating multiple sclerosis (Sorensen et al. 1999;Van Der Voorn et al. 1999), tumour (Arenberg et al. 1996, and in patients with Alzheimer's disease (Xia et al. 1998(Xia et al. , 2000, but also shown in neurons in physiological brain (Bajetto et al. 2001;Cartier et al. 2005). The latter favours the view that the chemokine receptor ligand family may have an important role in physiological cellular communication within the adult mammalian CNS. However, previous studies have provided far less information for understanding the physiological role of the chemokine Received April 5, 2006; revised manuscript received July 7, 2006; accepted October 3, 2006. Address correspondence and reprint requests to Dr Feng-Ru Tang, Epilepsy Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433. E-mail: Feng_Ru...

The dentate gyrus is a site of continued neurogenesis in the adult brain. The CA3 region of the hippocampus is the major projection area from the dentate gyrus. CA3 sends reciprocal projections back to the dentate gyrus. Does this imply that CA3 exerts some control over neurogenesis? We studied the effects of lesions of CA3 on neurogenesis in the dentate gyrus, and on the ability of fluoxetine to stimulate mitotic activity in the progenitor cells. Unilateral ibotenic-acid generated lesions were made in CA3. Four days later there was no change on the number of either BrdU or Ki67-positive progenitor cells in the dentate gyrus. However, after 15 or 28 days, there was a marked reduction in surviving BrdU-labelled cells on the lesioned side (but no change in Ki-67+ cells). pCREB or Wnt3a did not co-localise with Ki-67 but with NeuN, a marker of mature neurons. Lesions had no effect on the basal expression of either pCREB or Wnt3a. Subcutaneous fluoxetine (10 mg/kg/day) for 14 days increased the number of Ki67+ cells as expected on the control (non-lesioned) side but not on that with a CA3 lesion. Nevertheless, the expected increase in BDNF, pCREB and Wnt3a still occurred on the lesioned side following fluoxetine treatment. Fluoxetine has been reported to decrease the number of “mature” calbindin-positive cells in the dentate gyrus; we found this still occurred on the side of a CA3 lesion. We then showed that the expression GAP-43 was reduced in the dentate gyrus on the lesioned side, confirming the existence of a synaptic connection between CA3 and the dentate gyrus. These results show that CA3 has a hitherto unsuspected role in regulating neurogenesis in the dentate gyrus of the adult rat.

cPKA may play an important role in neuronal hyperexcitability, death and epileptogenesis during and after pilocarpine induced status epilepticus.