Aß(42) induced MRI changes in aged rabbit brain resembles AD brain.

Alzheimer's disease is the most common form of dementia and is structurally characterized by brain atrophy and loss of brain volume. Aß is one of the widely accepted causative factors of AD. Aß deposition is positively correlated with brain atrophy in AD. In the present study, structural brain imaging techniques such as Magnetic Resonance Imaging (MRI) were used to measure neuroanatomical alterations in Alzheimer's disease brain. MRI is a non-invasive method to study brain structure. The objective of the present study was to elucidate the role of Aß on brain structure in the aged rabbit brain. Among 20 aged rabbits, one batch (n=10) rabbits was injected chronically with Aß(1-42) and another batch (n=10) with saline. The MRI was conducted before Aß(1-42)/saline injection and after 45 days of Aß(1-42)/saline injection. All the aged rabbits underwent MRI analysis and were euthanized after 45 days. The MRI results showed a significant reduction in thickness of frontal lobe, hippocampus, midbrain, temporal lobe and increases in the lateral ventricle volume. We also conducted an MRI study on AD (n=10) and normal (n=10) cases and analyzed for the thicknesses of frontal lobe, hippocampus, midbrain, temporal lobe and lateral ventricle lobe. We found significant reductions in thickness of the frontal lobe and the hippocampus. However, no significant reduction in the thickness of midbrain, temporal lobe or increase in the lateral ventricle volume was observed compared to normal. Correlations in brain atrophy changes between rabbit brain and human AD brain were found for frontal lobe and hippocampal regions. In contrast, other regions such as midbrain, temporal lobe, and lateral ventricles were not correlated with rabbit brain atrophy changes in the corresponding regions. The relevance of these changes in AD is discussed.

Screening of Caesalpinia bonduc leaves for antipsoriatic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Caesalpinia bonduc (L.) Roxb. (Caesalpiniaceae) have been used by traditional Siddha healer of Malabar region for psoriasis treatment. AIM OF THE STUDY: To evaluate the Caesalpinia bonduc decoction (CBD), Caesalpinia bonduc hydroalcoholic extract (CBHA) for antipsoriatic activity. MATERIALS AND METHODS: Mouse tail test for psoriasis was used for the evaluation of antipsoriatic activity. Extracts were tested at a dose of 500 mg/kg b.w. and fractions at 250 mg/kg b.w. in Swiss albino mice. Parameters studied in the mouse tail test were changes in epidermal thickness and percentage orthokeratotic values. In vitro antiproliferant assay on HaCaT cell lines and in vitro lipoxygenase inhibition were also carried out. RESULTS: Butanol fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAB) and water fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAW) produced significant orthokeratosis (p<0.001). In relative epidermal thickness, a significant (p<0.05) reduction with respect to control was observed in groups treated with retinoic acid, CBD, butanol fraction of Caesalpinia bonduc decoction (CBDB), water fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAW). Maximum antiproliferant activity was shown by CBHA (IC(50), 77.5±12.7 µg/ml). In lipoxygenase inhibition assay, water fraction of Caesalpinia bonduc decoction (CBDW) showed maximum activity with an IC(50) value of 164.71±4.57 µg/ml. CONCLUSIONS: Among all the tested samples only CBHAW showed good activity in the mouse tail test, antiproliferant activity in HaCaT cells and lipoxygenase inhibition assay. Other extracts and fractions showed varying degrees of activity. The present study supports the traditional use of Caesalpinia bonduc leaves for psoriasis treatment.

Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression.

Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients' brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients' brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients' brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here.

New evidence on iron, copper accumulation and zinc depletion and its correlation with DNA integrity in aging human brain regions.

Deoxyribonucleic acid (DNA) conformation and stability play an important role in brain function. Earlier studies reported alterations in DNA integrity in the brain regions of neurological disorders like Parkinson's and Alzheimer's diseases. However, there are only limited studies on DNA stability in an aging brain and the factors responsible for genomic instability are still not clear. In this study, we assess the levels of Copper (Cu), Iron (Fe) and Zinc (Zn) in three age groups (Group I: below 40 years), Group II: between 41-60 years) and Group III: above 61 years) in hippocampus and frontal cortex regions of normal brains. The number of samples in each group was eight. Genomic DNA was isolated and DNA integrity was studied by nick translation studies and presented as single and double strand breaks. The number of single strand breaks correspondingly increased with aging compared to double strand breaks. The strand breaks were more in frontal cortex compared to hippocampus. We observed that the levels of Cu and Fe are significantly elevated while Zn is significantly depleted as one progresses from Group I to Group III, indicating changes with aging in frontal cortex and hippocampus. But the elevation of metals was more in frontal cortical region compared to hippocampal region. There was a clear correlation between Cu and Fe levels versus strand breaks in aging brain regions. This indicates that genomic instability is progressive with aging and this will alter the gene expressions. To our knowledge, this is a new comprehensive database to date, looking at the levels of redox metals and corresponding strand breaks in DNA in two brain regions of the aging brain. The biological significance of these findings with relevance to mental health will be discussed.

A new insight on Al-maltolate-treated aged rabbit as Alzheimer's animal model.

Lack of an adequate animal model for Alzheimer's disease (AD) has limited an understanding of the pathogenesis of the disease and the development of therapeutic agents targeting key pathophysiological processes. There are undoubtedly few satisfactory animal models for exploring therapies targeting at amyloid beta (Abeta) secretion, deposition, aggregation, and probably the inflammatory response. However, an understanding of the complex events--tau, Abeta, oxidative stress, redox active iron, etc.--involved in the neuronal cell loss is still unclear due to the lack of a suitable animal model system. The use of neurotoxic agents particularly aluminum-organic complexes, especially Al-maltolate, expands the scope of AD research by providing new animal models exhibiting neurodegenerative processes relevant to AD neuropathology. Examination of different species of aged animals including the rapidly advancing transgenic mouse models revealed very limited AD-like pathology. Most other animal models have single event expression such as extracellular Abeta deposition, intraneuronal neurofilamentous aggregation of proteins akin to neurofibrillary tangles, oxidative stress or apoptosis. To date, there are no paradigms of any animal in which all the features of AD were evident. However, the intravenous injection of Al-maltolate into aged New zealand white rabbits results in conditions which mimics a number of neuropathological, biochemical and behavioral changes observed in AD. Such neurodegenerative effects include the formation of intraneuronal neurofilamentous aggregates that are tau positive, immunopositivity of Abeta, presence of redox active iron, oxidative stress and apoptosis, adds credence to the value of this animal model system. The use of this animal model should not be confused with the ongoing controversy regarding the possible role of Al in the neuropathogenesis, a debate which by no means has been concluded. Above all this animal model involving neuropathology induced by Al-maltolate provides a new information in understanding the mechanism of neurodegeneration.