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Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

Little CS, Joyce TA, Hammond CJ, Matta H, Cahn D, Appelt DM, Balin BJ - Front Aging Neurosci (2014)

Bottom Line: The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months.Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41.These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine Philadelphia, PA USA ; Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine Philadelphia, PA, USA.

ABSTRACT
Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

No MeSH data available.


Related in: MedlinePlus

Recovery of viable Chlamydia pneumoniae from olfactory bulb and brain tissues following intranasal infection. (A) At 1, 3, and 4 months post-infection (pi), viable Cpn was recovered from olfactory bulb tissue homogenates of eight BALB/c mice, 3 of 3 mice at 1 month pi, 3 of 3 mice at 3 months pi, and 2 of 3 mice at 4 months pi. (B) In contrast, only 1 mouse demonstrated viable Cpn from cerebral cortical tissue at any time; that being one mouse at 3 months pi. Viable Cpn was quantified as infectious forming units/ml of tissue homogenate.
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Figure 1: Recovery of viable Chlamydia pneumoniae from olfactory bulb and brain tissues following intranasal infection. (A) At 1, 3, and 4 months post-infection (pi), viable Cpn was recovered from olfactory bulb tissue homogenates of eight BALB/c mice, 3 of 3 mice at 1 month pi, 3 of 3 mice at 3 months pi, and 2 of 3 mice at 4 months pi. (B) In contrast, only 1 mouse demonstrated viable Cpn from cerebral cortical tissue at any time; that being one mouse at 3 months pi. Viable Cpn was quantified as infectious forming units/ml of tissue homogenate.

Mentions: Olfactory bulbs and cerebral tissues were dissected from BALB/c mice following euthanization, snap-frozen, and homogenized prior to incubation with HEp-2 cells in culture to determine if detectable levels of viable Cpn could be recovered from the CNS. Ten-fold serial dilutions of the homogenized tissues were incubated with HEp-2 cells to determine the amount of viable infectious Cpn present in the tissues at 1, 3, and 4 months pi. Tissue from the 2 month animal was not available. Infectious Cpn was recovered and quantified from 3 of 3 olfactory bulbs at 1 month pi, ranging from 3 × 103 to 3 × 105 IFU/ml of tissue homogenate (Figure 1A). At 3 months pi, Cpn was detected in 3 of 3 olfactory bulbs with a range of 2 × 105 to 3 × 106 IFU/ml of tissue homogenate (Figure 1A). At 4 months, Cpn was detected in 2 of 3 olfactory bulbs with a range of 0 to 2 × 106 IFU/ml tissue homogenate (Figure 1A). Of the three olfactory bulbs tested from the mock-infected animals, no Cpn was recovered. In contrast to the olfactory bulbs, Cpn was not recovered from the brain tissue (cerebrum) at 1 and 4 months pi, although at 3 months, Cpn was recovered and quantified at 3 × 104 IFU/ml of tissue from 1 of 3 brains (Figure 1B). This same mouse had 3 × 105 IFU/ml in the olfactory bulb as noted above. With regards to brain tissues analyzed from the three control animals, no Cpn was detected.


Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

Little CS, Joyce TA, Hammond CJ, Matta H, Cahn D, Appelt DM, Balin BJ - Front Aging Neurosci (2014)

Recovery of viable Chlamydia pneumoniae from olfactory bulb and brain tissues following intranasal infection. (A) At 1, 3, and 4 months post-infection (pi), viable Cpn was recovered from olfactory bulb tissue homogenates of eight BALB/c mice, 3 of 3 mice at 1 month pi, 3 of 3 mice at 3 months pi, and 2 of 3 mice at 4 months pi. (B) In contrast, only 1 mouse demonstrated viable Cpn from cerebral cortical tissue at any time; that being one mouse at 3 months pi. Viable Cpn was quantified as infectious forming units/ml of tissue homogenate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257355&req=5

Figure 1: Recovery of viable Chlamydia pneumoniae from olfactory bulb and brain tissues following intranasal infection. (A) At 1, 3, and 4 months post-infection (pi), viable Cpn was recovered from olfactory bulb tissue homogenates of eight BALB/c mice, 3 of 3 mice at 1 month pi, 3 of 3 mice at 3 months pi, and 2 of 3 mice at 4 months pi. (B) In contrast, only 1 mouse demonstrated viable Cpn from cerebral cortical tissue at any time; that being one mouse at 3 months pi. Viable Cpn was quantified as infectious forming units/ml of tissue homogenate.
Mentions: Olfactory bulbs and cerebral tissues were dissected from BALB/c mice following euthanization, snap-frozen, and homogenized prior to incubation with HEp-2 cells in culture to determine if detectable levels of viable Cpn could be recovered from the CNS. Ten-fold serial dilutions of the homogenized tissues were incubated with HEp-2 cells to determine the amount of viable infectious Cpn present in the tissues at 1, 3, and 4 months pi. Tissue from the 2 month animal was not available. Infectious Cpn was recovered and quantified from 3 of 3 olfactory bulbs at 1 month pi, ranging from 3 × 103 to 3 × 105 IFU/ml of tissue homogenate (Figure 1A). At 3 months pi, Cpn was detected in 3 of 3 olfactory bulbs with a range of 2 × 105 to 3 × 106 IFU/ml of tissue homogenate (Figure 1A). At 4 months, Cpn was detected in 2 of 3 olfactory bulbs with a range of 0 to 2 × 106 IFU/ml tissue homogenate (Figure 1A). Of the three olfactory bulbs tested from the mock-infected animals, no Cpn was recovered. In contrast to the olfactory bulbs, Cpn was not recovered from the brain tissue (cerebrum) at 1 and 4 months pi, although at 3 months, Cpn was recovered and quantified at 3 × 104 IFU/ml of tissue from 1 of 3 brains (Figure 1B). This same mouse had 3 × 105 IFU/ml in the olfactory bulb as noted above. With regards to brain tissues analyzed from the three control animals, no Cpn was detected.

Bottom Line: The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months.Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41.These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine Philadelphia, PA USA ; Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine Philadelphia, PA, USA.

ABSTRACT
Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

No MeSH data available.


Related in: MedlinePlus