Table 3.

List of studies investigating tau protein in epilepsy.

S.N.	Study Type	Study Design	Observations	References
1	Experimental study	Intra-amygdala KA-induced SE in male C57BL6 rats	There was an upregulation of total tau levels and tau phosphorylation in the hippocampus post-SE. There was an elevation in tau phosphorylation during epilepsy at the AT8 epitope; however total tau expression was decreased in the hippocampus mainly in the CA3 and CA1 subfield.	[29]
2	Experimental study	KA (15 mg/kg, I.P.)-induced SE in male C57BL6 rats	There was a significant increase in the protein expression of tau kinase GSK3β in the ipsilateral hippocampus after SE.	[109]
3	Experimental study	Chronic acquired epilepsy induced by amygdala kindling and KA in male Wistar rats	Treatment with Sodium selenate decreased activity of PP2A, increased ratio of pS198 and pS262 immunoreactivity to tau-5 was observed in amygdala, hippocampus and cortex of both amygdala kindled and KA-induced SE rats. T-Tau levels remained uninfluenced in both the models.	[30]
4	Experimental study	KA (20 mg/kg, I.P.)-induced excitotoxicity damage in Male FVB mice	KA-induced excitotoxic damage leads to short-term tau hypophosphorylation followed by a gradual long-term hyperphosphorylation of tau. The initial dephosphorylation of tau in the first phase (within 6 h post-injection) might be due to PP2A activation and the gradual hyperphosphorylation of tau at later phase (after 6h post-injection) could be mainly due to CD5K activation and inhibition of PP2A during the second phase.	[107]
5	Experimental study	KA (30 mg/kg, I.P.)- induced SE in male CD10 mice	KA-induced SE leads to tau hyperphosphorylation, which might be due to increased activity of tau kinase (GSK3β, CDK5) and inactivation of AKT.	[108]
6	Clinical study	Drug-resistant TLE patients who had undergone anterior temporal lobe resection (n = 19)	Upregulation in the expression of tau 5 was observed in the TLE hippocampus but not in the temporal cortex. However, phospho-Tau AT180 was increased in both the hippocampus and temporal cortex of TLE patients. Among the tau isoforms containing 3 (3R) or 4 (4R) microtubules binding repeats, tau 3R expression was unaltered, but tau 4R expression was increased in TLE patients compared to the normal controls.	[28]
7	Clinical study	Patients TLE who had undergone anterior temporal lobe resection (n = 33)	Hyperphosphorylated tau (AT8 labelling) was mainly observed in the form of neuropil threads, NFTs and pre-tangles within the temporal lobe tissue. 31 out of 33 TLE patients exhibited AT8 labelling.	[111]
8	Clinical study	Patients with tonic-clonic or partial secondarily generalized seizures are considered (n = 54)	The median T-Tau and p-Tau was 163.1 pg/mL and 39.6 pg/mL respectively in the patients whereas for the control the value of T-Tau and p-Tau was 143.5 pg/mL and 38.1 pg/mL respectively. However, there was no significance difference between the groups. There was significant difference between ration of T-Tau/p-Tau between epileptic and control group.	[110]

KA, Kainic acid; TLE, Temporal lobe epilepsy; SE, SE, Status Epilepticus; GSK3β, Glycogen synthase kinase-3β; PP2A, Protein phosphatase 2A; AKT, Protein kinase B; CDK5, Cyclin-dependent kinase 5; NFTs, Neurofibrillary tangles; CA3, Cornu Ammonis 3; CA1, Cornu Ammonis 1; T-Tau, Total tau; P-Tau, Phosphorylated tau.