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Table 2 Proposed physiological roles of cellular prion protein

From: The biological function of the cellular prion protein: an update

Role of PrPC in Phenotype of Prnp -/- model system Report (mouse model/cell line used) Contradictory reports
Synaptic transmission and plasticity Reduced long-term potentiation [58] (ZH1)
[29] (Edgb)
[61] (ZH1, other a)
[98] (ZH1)
Reduced excitatory and inhibitory synaptic transmission [58] (ZH1)
[62] (ZH1, Ngsk)
[61] (ZH1, other a)
[147] (ZH1)
Memory formation Reduced spatial learning and memory [64] (other b) [28] (ZH1)
Reduced avoidance learning and memory [65] (ZH1)
[148] (Ngsk)
[68] (ZH1)
Stabilization of sleep and circadian rhythm Altered circadian rhythm, increased sleep fragmentation, increased SWA after sleep deprivation [71] (ZH1, Edgb) [74] (Other b)
Neuronal excitability Reduced Kv4.2 currents [77] (ZH1, HEK293T)  
Reduced sAHP and calcium-activated potassium currents [79] (ZH1)
[80] (ZH1)
[82] (ZH1)
[39] (Tg35)
[83] (ZH1)
Increased susceptibility to Kainate-induced seizures [84] (ZH1) [41] (Other b)
Calcium homeostasis Reduced VGCC currents [80] (ZH1) [83] (ZH1)
Increased calcium buffering [83] (ZH1)
Glutamate receptor function Increased NMDA currents, nociception and depressive-like behavior [90] (ZH1)
[91, 92] (ZH1)
Upregulation of Kainate receptor subunits [84] (ZH1)
Neurite outgrowth Delayed development of cerebellar circuitry [120] (ZH1)  
Reduced neurite outgrowth in vitro [106] (ZH1)
Toxicity elicited by oligomeric species Protected from LTP reduction induced by toxic Aβ species [98] (ZH1, other c) [102] (ZH1)
[103] (ZH1)
[104] (Other b)
[105] (Other a)
Neuroprotection Larger lesions in model of acute cerebral ischemia [122] (ZH1)
[123] (ZH1)
[124] (ZH1)
Decreased SOD activity [133] (ZH1) [135] (ZH1)
Copper, zinc, iron, and lactate metabolism Reduced zinc content in primary neurons [95] (ZH1, SH-SY5Y)  
Increased lactate-uptake in cultured astrocytes [96] (ZH1)
Altered iron and copper metabolism [139] (Other a)
Peripheral myelin maintenance Age-dependent demyelinating neuropathy [141] (ZH1, Edgb)
[42] (ZH3)
  1. Bold indicates mixed genetic background of at least two distinct mouse strains, possibly leading to the “flanking-gene problem”. Italic indicates mice maintained on single, pure genetic background. Mouse lines specified as “other” are: aZH1 backcrossed to FVB; bEdgb (back-)crossed to C57BL/10; cEdbg backcrossed to C57BL6