Haemoglobins are iron-containing proteins that transport oxygen in the blood of most vertebrates. The mitochondrion is the cellular organelle which consumes oxygen in order to synthesise ATP. Mitochondrial dysfunction is implicated in neurodegeneration and ageing. We find that α and β haemoglobin (Hba and Hbb) proteins are altered in their distribution in mitochondrial fractions from degenerating brain. We demonstrate that both Hba and Hbb are co-localised with the mitochondrion in mammalian brain. The precise localisation of the Hbs is within the inner membrane space and associated with inner mitochondrial membrane. Relative mitochondrial to cytoplasmic ratios of Hba and Hbb show changing distributions of these proteins during the process of neurodegeneration in the pcd5j mouse brain. A significant difference in mitochondrial Hba and Hbb content in the mitochondrial fraction is seen at 31 days after birth, this corresponds to a stage when dynamic neuronal loss is measured to be greatest in the Purkinje Cell Degeneration mouse. We also report changes in mitochondrial Hba and Hbb levels in ageing brain and muscle. Significant differences in mitochondrial Hba and Hbb can be seen when comparing aged brain to muscle, suggesting tissue specific functions of these proteins in the mitochondrion. In muscle there are significant differences between Hba levels in old and young mitochondria. To understand whether the changes detected in mitochondrial Hbs are of clinical significance, we examined Parkinson's disease brain, immunohistochemistry studies suggest that cell bodies in the substantia nigra accumulate mitochondrial Hb. However, western blotting of mitochondrial fractions from PD and control brains indicates significantly less Hb in PD brain mitochondria. One explanation could be a specific loss of cells containing mitochondria loaded with Hb proteins. Our study opens the door to an examination of the role of Hb function, within the context of the mitochondrion—in health and disease.

Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles.To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p < 0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post-mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n = 7). The change is less discernible in male cerebellum (n = 18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle.These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease.

An 8-year-old male intact miniature poodle presented for blindness, obtundation, tetraparesis and vestibular signs. Magnetic resonance imaging (MRI), radiography and ultrasound revealed a left piriform lobe lesion, right cerebellar and left brainstem lesions, hydrocephalus and bilateral calvarial defects. Histopathology confirmed a choroid plexus carcinoma with meningeal and intraventricular metastases. The calvarial defect did not show evidence of necrosis, osteoclastic resorption, inflammation or neoplastic infiltration, reflecting a quiescent calvarial atrophy or dysplasia. The imaging characteristics are indicative of calvarial atrophy secondary to chronic increased intracranial pressure and this is the first report of a calvarial defect of this size.

A 5-year-old, male, neutered lurcher dog was presented for investigation of a cranial abdominal mass and suspected acute pancreatitis. Advanced diagnostic imaging revealed the presence of a cavitated mass, multiple splenic nodules and coeliac lymphadenopathy. Fluid analysis from ultrasound-guided mass-lesion aspiration was suggestive of a pancreatic origin. After medical stabilisation, the dog underwent celiotomy where partial left limb pancreatectomy, splenectomy and coeliac lymphadenectomy were performed. Histopathological examination was consistent with a chronic pancreatic haematoma, splenic nodular hyperplasia with sinus histiocytosis and sinus erythrocytosis of the coeliac lymph node. Post-operatively, the dog recovered rapidly with supportive care. Re-examination 3 months later showed that it remained clinically normal with no symptoms of pancreatitis, and no evidence of recurrence of the haematoma or metastatic disease. This report describes the presentation of a large pancreatic lesion, compatible with a haematoma, and its successful surgical treatment in a dog.

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A 7-year-old male neutered cocker crossbreed was presented with a 1-month history of tachypnoea and exercise intolerance. Initial investigations confirmed a pleural effusion due to a mediastinal T-cell lymphoma. L-asparaginase and a 23-week lomustine, vincristine, prednisolone protocol were pursued and complete response was recorded at the end of the protocol. Ten months later, he was presented at the referring veterinary practice with a non-bearing lameness of his left forelimb, and a transcondylar screw was placed following the suspicion of a fracture of the lateral humeral epicondyle. During surgery, a sample of bone was collected and submitted for histopathology. Histopathology and immunohistochemistry were consistent with a T-cell lymphoma. Total body CT scan revealed a monostotic aggressive lesion of the distal humerus with no evidence of infiltration into bone at any other sites, and no other signs of lymphoma relapse were seen elsewhere in the body. Based on these findings, secondary bone lymphoma was hypothesised.

A five-year-old, male entire Jack Russell terrier presented for a two-month history of ambulatory paraparesis lateralised to the left. Neurological examination localised to an L4–S3 myelopathy. MRI revealed an equivocal intramedullary lesion at the level of the L4–L5 disc space occupying 80 per cent of the spinal cord area. The mass was surgically resected. Histopathology confirmed the mass to be consistent with a meningioma in which a high proportion of neoplastic cells exhibited clear cytoplasm that stained positively with periodic acid-Schiff and was diastase-sensitive. This mass was assigned grade II/atypical (World Health Organization human system) based on the predominant clear cell morphology and a mitotic count of 10 mitotic figures in 10 high-power fields. To the authors’ knowledge, this is the first reported case of a clear cell meningioma in a dog.

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