Newly developed TGF-ß2 knock down transgenic mouse lines express TGF-ß2 differently and its distribution in multiple tissues varies.

BACKGROUND: Transforming growth factor-betas (TGF-ßs), including beta2 (TGF-ß2), constitute a superfamily of multifunctional cytokines with important implications in morphogenesis, cell differentiation and tissue remodeling. TGF-ß2 is thought to play important roles in multiple developmental processes and neuron survival. However, before we carried out these investigations, a TGF-ß2 gene down-regulated transgenic animal model was needed. In the present study, expressional silencing TGF-ß2 was achieved by select predesigning interference short hairpin RNAs (shRNAs) targeting mouse TGF-ß2 genes. RESULTS: Four homozygous transgenic offspring were generated by genetic manipulation and the protein expressions of TGF-ß2 were detected in different tissues of these mice. The transgenic mice were designated as Founder 66, Founder 16, Founder 53 and Founder 41. The rates of TGF-ß2 down-expression in different transgenic mice were evaluated. The present study showed that different TGF-ß2 expressions were detected in multiple tissues and protein levels of TGF-ß2 decreased at different rates relative to that of wild type mice. The expressions of TGF-ß2 proteins in transgenic mice (Founder 66) reduced most by 52%. CONCLUSIONS: The present study generated transgenic mice with TGF-ß2 down-regulated, which established mice model for systemic exploring the possible roles of TGF-ß2 in vivo in different pathology conditions.

Evodiamine improves congnitive abilities in SAMP8 and APP(swe)/PS1(ΔE9) transgenic mouse models of Alzheimer's disease.

AIM: To investigate the effect of evodiamine (a quinolone alkaloid from the fruit of Evodia rutaecarpa) on the progression of Alzheimer's disease in SAMP8 and APP(swe)/PS1(ΔE9) transgenic mouse models. METHODS: The mice at age of 5 months were randomized into the model group, two evodiamine (50 mg·kg(-1)·d(-1) and 100 mg·kg(-1)·d(-1)) groups and an Aricept (2 mg·kg(-1)·d(-1)) group. The littermates of no-transgenic mice and senescence accelerated mouse/resistance 1 mice (SAMR1) were used as controls. After 4 weeks of treatment, learning abilities and memory were assessed using Morris water-maze test, and glucose uptake by the brain was detected using positron emission tomography/computed tomography (PET/CT). Expression levels of IL-1ß, IL-6, and TNF-α in brain tissues were detected using ELISA. Expression of COX-2 protein was determined using Western blot. RESULTS: In Morris water-maze test, evodiamine (100 mg·kg(-1)·d(-1)) significantly alleviated the impairments of learning ability and memory. Evodiamine (100 mg·kg(-1)·d(-1)) also reversed the inhibition of glucose uptake due to development of Alzheimer's disease traits in mice. Furthermore, the dose of evodiamine significantly decreased the expression of IL-1ß, IL-6, TNF-α, and COX-2 that were involved in the inflammation due to Alzheimer's disease. CONCLUSION: The results indicate that evodiamine (100 mg·kg(-1)·d(-1)) improves cognitive abilities in the transgenic models of Alzheimer's disease.

Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2.

The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age. The messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed the SCN2B expressions in the prefrontal cortex, resulting in improved learning and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level by 60.68% resulted in improvement in the hippocampus-dependent spatial recognition memory and long-term potential (LTP) slope of field excitatory postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression. Together, the present findings indicated that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of COX5A and FGF-2. These findings could provide the potential strategy of candidate target to develop antisenescence drugs for the treatment of brain aging.

Expressional difference, distributions of TGF-ß1 in TGF-ß1 knock down transgenic mouse, and its possible roles in injured spinal cord.

Transforming growth factor ß1 (TGF-ß1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-ß1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-ß1 was achieved by selecting predesigning hairpins targeting mouse TGF-ß1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-ß1 in different transgenic mice were also determined. To investigate the potential roles of TGF-ß1, we observed changes in the neurological behavior of TGF-ß1-knockdown (TGF-ß1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-κB and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-ß1 expressions were detected in multiple tissues, and protein levels of TGF-ß1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-ß1 proteins in TGF-ß1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-ß1 down regulated mice and determine the possible roles of TGF-ß1 in vivo in different conditions.