Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

Abstract

Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.

RETRACTED ARTICLE: Early Minocycline and Late FK506 Treatment Improves Survival and Alleviates Neuroinflammation, Neurodegeneration, and Behavioral Deficits in Prion-Infected Hamsters

“…Inflammation is a common event in several neurodegenerative diseases and has been recently implicated as a key mechanism responsible for the progressive nature of these disorders. As such, controlling inflammation is regarded as a possible effective therapeutic approach [13,28]. Consistent with previous reports [3,28], our data showed a significant increase in astrocyte activation in prion-vehicle animals (group A) compared with the control group (group E) and further reveal that this phenomenon can be prevented by minocycline or FK506 treatment.…”

“…As such, controlling inflammation is regarded as a possible effective therapeutic approach [13,28]. Consistent with previous reports [3,28], our data showed a significant increase in astrocyte activation in prion-vehicle animals (group A) compared with the control group (group E) and further reveal that this phenomenon can be prevented by minocycline or FK506 treatment. Microglia, the brain innate immune cells, are activated in response to the accumulation of misfolded proteins resulting in neuroinflammation and subsequent neurodegeneration [13].…”

“…However, the survival of animals receiving minocycline after the appearance of clinical signs did not differ from that of animals in the prion-vehicle and prion-FK506 early groups (groups A and B, respectively), suggesting that late treatment with minocycline may be ineffective (data not shown). These findings suggest that the mechanisms of protection from prion with minocycline may involve reducing early neuroinflammation and subsequent neurodegeneration, which would be consistent with previous literature evidence [28,64,71,72].…”

“…Animals in group D were injected i.p. with 0.36 mg minocycline (15 mg/kg) dissolved in 100 ml of the vehicle solution mentioned above according to previous experiments [27][28][29]. Minocycline stock solution was stored frozen in a light-protected bottle.…”

The effects of minocycline on hippocampus in lithium-pilocarpine induced status epilepticus in rat: relations with microglial/astrocytic activation and serum s100b level

“…Scopolamine can inhibit SE when administered before pilocarpine but is not effective after SE has been established (7). Because methylscopolamine cannot cross the BBB, it is used to reduce the peripheral muscarinic adverse effects of pilocarpine (8). However, methylscopolamine may have crossed the BBB due to greater permeability after neuroinflammation, thereby possibly contributing to the inhibition of recurrence in our study (10)(11)(12).…”