gms | German Medical Science

Seizure-associated dysregulation of excitatory and inhibitory peptides has been observed in laboratory animals and humans likewise and may account for epileptogenicity and disease progression. Amongst these, Neuropeptide Y (NPY) inhibits hippocampal glutamatergic synaptic transmission while Substance P (SP) exerts pro-epileptic effects and has been associated with status epilepticus.

In order to approach the relevance of neuropeptide dysregulation in feline epilepsy we elucidated expression of Neuropeptide Y (NPY) and Substance P (SP) within the mesial temporal lobe of cats with epilepsy-associated hippocampal sclerosis (HS).

The immunohistochemical pattern of NPY and SP expression was assessed in 26 feline brains with HS and compared to age-matched non-neurologic controls. Analytical algorithms focussed on topography of NPY and SP positive cells within dentate gyrus, cornu ammonis segments (CA) and parahippocampal gyrus (PHG), its subcellular distribution (synaptic, dendritic, perikaryal) and signal intensity.

NPY in epileptic and control animals was localized to perikarya, apical dendrite and synaptic terminals addressing pyramidal neurons and dentate gyrus granular cells. SP was expressed in the same regions at synaptic level only. Synaptic NPY signal was decreased in CA4 and stratum radiatum of CA2 and CA1 (p≤0.05) of HS patients. Degenerating neurons consistently stained strongly NPY-positive (p≤0.001) independent of the CA-segment. SP was significantly decreased in HS compared to controls in CA3, CA2, CA1 and PHG.

Decrease of both synaptic NPY and SP expression in epileptic cats may be due to either loss of synapses and neuronal loss, in course of HS, or depletion of the readily releasable pool of the presynapse due to exaggerated release. Assessment of candidate peptides for neuromodulation in a species with naturally developing epilepsy may contribute to development of new therapies to assist conventional antiepileptic treatments.